首页|Impact of obese levels on the hepatic expression of nuclear receptors and drug-metabolizing enzymes in adult and offspring mice

Impact of obese levels on the hepatic expression of nuclear receptors and drug-metabolizing enzymes in adult and offspring mice

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The prevalence of obesity-associated conditions raises new challenges in clinical medication.Although altered expression of drug-metabolizing enzymes (DMEs) has been shown in obesity,the impacts of obese levels (overweight,obesity,and severe obesity) on the expression of DMEs have not been elucidated.Especially,limited information is available on whether parental obese levels affect ontogenic expression of DMEs in children.Here,a high-fat diet (HFD) and three feeding durations were used to mimic different obese levels in C57BL/6 mice.The hepatic expression of five nuclear receptors (NRs) and nine DMEs was examined.In general,a trend of induced expression of NRs and DMEs (except for Cvp2c29 and 3a11) was observed in HFD groups compared to low-fat diet (LFD) groups.Differential effects of HFD on the hepatic expression of DMEs were found in adult mice at different obese levels.Family-based dietary style of an HFD altered the ontogenic expression of DMEs in the offspring older than 15 days.Furthermore,obese levels of parental mice affected the hepatic expression of DMEs in offspring.Overall,the results indicate that obese levels affected expression of the DMEs in adult individuals and that of their children.Drug dosage might need to be optimized based on the obese levels.

Diet-induced obesityOverweightHigh-fat dietDrug-metabolizing enzymesNuclear receptorsOntogenic expression

Pei Wang、Xueyan Shao、Yifan Bao、Junjie Zhu、Liming Chen、Lirong Zhang、Xiaochao Ma、Xiao-bo Zhong

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Department of Pharmacology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001,China

Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, CT 06269, USA

Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA 15261,USA

This work was supported by the National Institutes of HealthThis work was supported by the National Institutes of HealthPei Wang was supported by the China Scholarship Council

Grant R01GM118367 to Xiao-bo ZhongUSAGrant 201707040007

2020

药学学报(英文版)

药学学报(英文版)

CSTPCDCSCDSCI
ISSN：
年,卷(期)：2020.10(1)
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